Figure 7. Model for Laminin-211 and GPR126 interactions in SC development.
Our data support a model in which Laminin-211 interacts with GPR126-NTF to stabilize the receptor in an inactive state. This prevents cAMP accumulation through suppression of basal GPR126 Gs signaling and allows the SC to remain in an immature state for radial sorting. Independent of Gpr126-CTF, Gpr126-NTF is required for radial sorting. Following BL maturation and Laminin-211 polymerization, Laminin-211 facilitates an active Gs signaling conformation of GPR126-CTF. This may be accomplished by removal of GPR126-NTF via mechanical forces induced during Laminin-211 polymerization. Gs signaling promotes cAMP accumulation, downstream signaling, and terminal differentiation of the SC.